U.S. patent number 4,888,482 [Application Number 07/175,264] was granted by the patent office on 1989-12-19 for atmospheric pressure ionization mass spectrometer.
This patent grant is currently assigned to Hitachi, Ltd.. Invention is credited to Yoshiaki Kato.
United States Patent |
4,888,482 |
Kato |
December 19, 1989 |
Atmospheric pressure ionization mass spectrometer
Abstract
An atmospheric pressure ionization mass spectrometer includes an
ionization unit having corona discharge mechanism for introducing
thereto gaseous mobile phase molecules and gaseous solute molecules
and ionizing the mobile phase molecules through corona discharge
under an atmosphere of the mobile phase molecules and the solute
molecules; an ion reaction unit for ionizing the solute molecules
through molecular ion reaction of the ionized mobile phase
molecules with the solute molecules; and an ion analysis unit for
mass analyzing the ionized solute molecules; wherein the corona
discharge mechanism comprises a discharge electrode for conducting
corona discharge at a plurality of points, and a DC power supply
for applying a DC voltage to the discharge electrode.
Inventors: |
Kato; Yoshiaki (Mito,
JP) |
Assignee: |
Hitachi, Ltd. (Tokyo,
JP)
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Family
ID: |
13608863 |
Appl.
No.: |
07/175,264 |
Filed: |
March 30, 1988 |
Foreign Application Priority Data
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Mar 30, 1987 [JP] |
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62-76569 |
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Current U.S.
Class: |
250/281;
250/423F; 250/288 |
Current CPC
Class: |
H01J
49/26 (20130101) |
Current International
Class: |
H01J
49/26 (20060101); H01J 049/26 () |
Field of
Search: |
;250/281,282,288,288A,423R,423F |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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1171641 |
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Aug 1961 |
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DE |
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57-25944 |
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Jun 1982 |
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JP |
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1442998 |
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Jul 1976 |
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GB |
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Other References
"High-Rate Growth of Dendrites on Thin Wire Anodes for Field
Desorption Mass Spectrometry", Linden et al., J. Phys. E. Sci.
Inst., vol. 11, 1978, pp. 1033-1036. .
Thomas R. Covey et al, "Liquid Chromatography/Mass Spectrometry",
Analytical Chemistry, vol. 58, No. 14, Dec. 1986, pp. 1451-1461.
.
E. C. Horning et al, "Liquid Chromatograph-Mass
Spectrometer-Computer Analytical Systems, A Continuous-Flow System
Based on Atmospheric Pressure Ionization Mass Spectrometry",
Journal of Chromatography 99, 1974, pp. 13-21, p. 15..
|
Primary Examiner: Anderson; Bruce C.
Attorney, Agent or Firm: Antonelli, Terry & Wands
Claims
I claim:
1. An atmospheric pressure ionization mass spectrometer
comprising:
an ionization unit having corona discharge means for introducing
thereto gaseous mobile phase molecules and gaseous solute
molecules, and ionizing said mobile phase molecules through corona
discharge under an atmosphere of said mobile phase molecules and
said solute molecules;
an ion reaction unit for ionizing said solute molecules through
molecular ion reaction of said ionized mobile phase molecules with
said solute molecules; and
an ion analysis unit for mass analyzing said ionized solute
molecules;
wherein said corona discharge means comprises discharge electrode
means for conducting corona discharge at a plurality of points, and
a DC power supply for applying a DC voltage to said discharge
electrode means.
2. An atmospheric pressure ionization mass spectrometer according
to claim 1, wherein said discharge electrode means comprises an
assembly of a plurality of needle electrodes.
3. An atmospheric pressure ionization mass spectrometer according
to claim 1, wherein said discharge electrode means is a
circumferential surface of a fine conductive wire whose diameter is
in the range of about 20 to 100 .mu.m.
4. An atmospheric pressure ionization mass spectrometer according
to claim 1, wherein said discharge electrode means comprises a
plurality of whiskers formed on a periphery of a fine conductive
wire.
5. An atmospheric pressure ionization mass spectrometer according
to claim 1, wherein said discharge electrode means comprises a
knife edge portion.
6. An atmospheric pressure ionization mass spectrometer
comprising:
a liquid chromatograph for separating a liquid mixture of a
specimen and eluting therefrom liquid mobile phase molecules and
liquid solute molecules;
vaporizing means for vaporizing said eluted liquid mobile phase
molecules and liquid solute molecules;
an ionization unit having corona discharge means for introducing
thereto gaseous mobile phase molecules and gaseous solute molecules
and ionizing said mobile phase molecules through corona discharge
under an atmosphere of said mobile phase molecules and said solute
molecules;
an ion reaction unit for ionizing said solute molecules through
molecular ion reaction of said ionized mobile phase molecules with
said solute molecules; and
an ion analysis unit form ass analyzing said ionized solute
molecules;
wherein said corona discharge means comprises discharge electrode
means for conducting corona discharge at a plurality of points of
said discharge means, and a DC power supply for applying a DC
voltage to said discharge electrode means.
7. An atmospheric pressure ionization mass spectrometer according
to claim 6, wherein said discharge electrode means comprises an
assembly of a plurality of needle electrodes.
8. An atmospheric pressure ionization mass spectrometer according
to claim 6, wherein said discharge electrode means is a
circumferential surface of a fine conductive wire whose diameter is
in the range of about 20 to 100 .mu.m.
9. An atmospheric pressure ionization mass spectrometer according
to claim 6, wherein said discharge electrode means comprises a
plurality of whiskers formed on a periphery of a fine conductive
wire.
10. An atmospheric pressure ionization mass spectrometer according
to claim 6, wherein said discharge electrode means comprises a
knife edge portion.
Description
BACKGROUND OF THE INVENTION
The present invention relates to a mass spectrometer and more
particularly, to an atmospheric pressure ionization mass
spectrometer capable of correctly analyzing a mass of solutes even
under an atmosphere containing a large amount of absorptive
substances such as organic compounds.
A liquid chromatograph (hereinafter simply called "LC") is a means
for separating mixtures with excellent results, but it has a very
poor capability of identifying compounds, i.e., a very poor
qualitative performance. On the other hand, a mass spectrometer
(hereinafter simply called "MS") has an excellent qualitative
performance, but it cannot be used in analyzing mixtures. It
becomes possible to analyze mixtures if LC and MS are directly
coupled together. However, since MS analyzes samples in vacuum
conditions, liquids directly introduced to MS cannot undergo the
analysis, thus necessiating an interface between LC and MS.
Atmospheric Pressure Ionization (API) has been proposed heretofore
as such an interface. Examples of an atmospheric pressure
ionization mass spectrometer using API are shown, for example, in
No. JP-B-57-25944; Thomas R. Covey et al., "Liquid
Chromatography/Mass Spectrometry", ANALYTICAL CHEMISTRY, Vol. 58,
No. 14, Dec. 1986, p. 1456; and E. C. Horning et al., "Liquid
Chromatograph-Mass Spectrometer-Computer Analytical Systems, A
Continuous-Flow System Based on Atmospheric Pressure Ionization
Mass Spectrometry", Journal of chromatography, 99, 1974, 13-21, p.
15.
FIG. 1 is a block diagram of a liquid chromatograph-mass
spectrometer (LC/MS) analytical system, corresponding to that shown
in FIG. 1, p. 15 of "Journal of Chromatography", to which the
present invention is applied.
As shown in FIG. 1, an effluent of mobile phase and solutes from LC
1 is introduced to an LC/MS interface 2 wherein the effluent is
first vaporized at a spray/vapor chamber 3 and directed to an ion
source unit 4. The molecular solutes are ionized at the ion source
unit 4, and introduced to an ion analysis unit 5 made of a mass
spectrometer (MS) to be mass analyzed. The ion source unit 4 and
the ion analysis unit 5 constitute an atmospheric pressure
ionization mass spectrometer one example thereof described in No.
JP-B-57-25944 being shown in FIG. 2.
Referring to FIG. 2, reference numeral 11 denotes an inlet for
sample gas, 12 an ionization section, 13 a molecular ion reaction
chamber, 5 an ion analysis unit, 15 a corona discharge needle
electrode for ionizing sample gas, 17 a secondary electron
multiplier for use in detecting ions, 18 an auxiliary electrode
having a first small aperture 20a (e.g., 200 .mu.m in diameter), 21
an electron gun, 22 an electron beam control electrode, 23 an ion
attraction and acceleration electrode, 24 an ion lens electrode, 14
a variable DC voltage source with an output of 4 to 5 kV, 16 a
quadrupole, 26 a DC amplifier, and 28 a data processor.
The molecular ion reaction chamber 13 is connected to a vacuum pump
(not shown) and also acts as a room for differential pumping.
The electron gun 21 is used for electron bombardment for the
calibration of ion mass.
Using the above atmospheric pressure ionization mass spectrometer
will be described, by way of example, how organic compounds
contained in nitrogen gas are analyzed at an atmospheric pressure.
Corona discharge between the corona discharge needle electrode 15
and the auxiliary electrode 18 within the ionization unit 12 causes
nitrogen gas to be ionized into nitrogen ions which are introduced
into the molecular ion reaction chamber 13. In the molecular ion
reaction chamber 13, nitrogen ions are subjected to molecular ion
reaction with a minute amount of water in the order of several ppm
contained in nitrogen gas, to thereby produce H.sub.3 O.sup.+ ions
which are subjected to molecular ion reaction with organic
compounds likely to be ionized and contained in nitrogen gas to
ionize them. A small amount of organic compound ions thus produced
are introduced via the small aperture 20a into the ion analysis
unit 5 to be separated and analyzed.
Conventional atmospheric pressure mass spectrometers of this type
have an excellent sensitivity in detecting a minute amount of
components contained in a gas, but they cannot be used in analyzing
a specimen containing a large amount of absorptive substances such
as organic compounds. The reason for this is that a large amount of
organic compounds contained in the gas are deposited on the needle
electrode generating corona discharge, and are changed in to
macromolecule compounds of insulative nature, thereby leading to
unstable discharge. Namely, deposition of insulative macromolecule
compounds on the needle electrode decreases a corona current and
reduces ion current output. In the meantime, the potential of the
needle electrode rises to ultimately result in dielectric breakdown
and an abrupt rise in ion current output.
Therefore, as corona discharge becomes unstable, ion current output
also becomes unstable so that it is difficult to stably conduct
chromatography and mass spectrometry, with the essential high
sensitivity of API impaired.
Different from the ionization of impurities in pure gas, an LC/MS
system transports a liquid in the amount of several ml/minute to
several l/minute so that after vaporization it changes to a volume
from several l/minute to several ml/minute. Consequently, the
needle electrode 15 is likely to be contaminated with organic
compounds or the like.
The spectrometer shown in FIG. 3 was used in measuring an output
ion current I, i.e., an output current from the DC amplifier 26,
using lipids such as monogalactosyl diacyl glycerol as specimen to
be analyzed, the measurement result being shown in FIG. 3. As
apparent from FIG. 3, the output ion current unstably fluctuated
between a range of about .DELTA.I so that, of the main components
(1) to (5) of the specimen the components (4) and (5) with a low
output ion current, could not be detected.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an atmospheric
pressure ionization mass spectrometer capable of stably generating
corona discharge even under an atmosphere containing a large amount
of absorptive substances such as organic compounds and thereby
analyzing a specimen stably and with high sensitivity.
To achieve the above object, the corona discharge mechanism of an
ionization unit uses an electrode which can discharge at a
plurality of points, instead of using a single needle
electrode.
In particular, a discharge electrode has an increased number of
corona discharge points to thereby permit corona discharge to occur
at plural positions of the electrode. Therefore, even if organic
compounds are deposited on one of the discharge points of the
electrode, the remaining discharge points continue the corona
discharge so that the electrode as a whole can hold stable corona
discharge. In addition, even if one of the discharge points of the
electrode stops its discharge due to deposition of organic
compounds, the potential of the stopped discharge point of the
electrode rises while the remaining discharge points continue the
corona discharge, so that the deposited compounds are destroyed and
dispersed by discharge breakdown and the stopped discharge point
accordingly resumes corona discharge.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram showing a liquid chromatograph-mass
spectrometer (LC/MS) analytical system to which the present
invention is applied;
FIG. 2 shows an example of a conventional atmospheric pressure
ionization mass spectrometer;
FIG. 3 shows one example of a measurement result of a specimen with
the mass spectrometer shown in FIG. 2;
FIG. 4 shows an embodiment of an atmospheric pressure ionization
mass spectrometer according to the present invention;
FIGS. 5A and 5B are side and front views showing an embodiment of a
discharge electrode according to the present invention;
FIG. 6 shows one example of a measurement result with the mass
spectrometer according to the present invention;
FIGS. 7A and 7B are side and front views showing another example of
a discharge electrode used in the present invention;
FIGS. 8A, 8B and 8C are side, front and enlarged views showing a
further example of a discharge electrode used in the present
invention; and
FIGS. 9A and 9B are side and front views showing a still further
example of a discharge electrode used in the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Typical embodiments of an atmospheric pressure ionization mass
spectrometer according to the present invention will be described
with reference to the accompanying drawings.
FIG. 4 shows an embodiment of an atmospheric pressure ionization
mass spectrometer according to the present invention, wherein
elements having similar function to those shown in FIG. 2 are
represented by using identical reference numerals, and the
description therefor is omitted.
The pressure is preferably 10.sup.3 pascal in an ionization unit
12, 20 pascal at a molecular ion reaction chamber 13, and
2.times.10.sup.-3 pascal at an ion analysis unit 5.
In this embodiment, a discharge electrode 25 or corona discharge
mechanism serving as ionization means in the ionization unit 12, is
constructed as shown in FIGS. 5A and 5B. Namely, as shown enlarged
in FIGS. 5A and 5B, the discharge electrode 25 is constructed of an
assembly of a plurality of needle electrodes 31, the tip of each
needle electrode serving as a discharge point so that the discharge
electrode as a whole discharges at plural points. The number of
needle electrodes may be two at a minimum, but it is preferable to
have ten or more needle electrodes for the purpose of stable corona
discharge. Each needle electrode 31 may preferably be a tungsten
wire, a rhenium wire or a stainless wire having a diameter of about
50 .mu.m and a length of about 30 mm, all the needle electrodes
being bundled together, inserted into a stainless tube 30 having an
inner diameter of about 1.0 mm to 1.5 mm, and fixed in place by
squeezing the stainless tube. The finished discharge electrode
constitutes a multiple point discharge electrode. Each tip of the
needle electrode 31 has a sharp edge, with distance between
adjacent tips not needed to be limited specifically.
Organic compounds particularly suitable for a specimen of the
present invention include carbo hydrate, peptide, lipid and the
like. Mobile phase or solvents include water, methanol,
acetonitrile and the like.
The operation of the embodiment spectrometer applied to the LC/MS
system shown in FIG. 1 will now be described. A mobile phase
(liquid; containing a large amount of organic compound effluent
from LC 1 is vaporized at a spray/vapor chamber 3 and introduced
via an inlet 11 to an ion source unit 4. A voltage of 3 to 9 kV is
applied to the multiple point discharge electrode of the ion source
unit 4 so that the mobile phase is ionized in the ionization unit
12 under corona discharge.
The ionized mobile phase is introduced to the molecular ion
reaction chamber 13 to be subjected to molecular ion reaction with
solutes such as organic compounds. The ionized organic compounds
are mass analyzed in the ion analysis unit 5.
Organic compounds present in the ionization unit 12 to a large
extent are deposited on the discharge electrode 25. However, the
discharge electrode is an assembly of a plurality of needle
electrodes 31 so that even if some of the needle electrodes 31 are
deposited with organic compounds, the remaining needle electrodes
continue corona discharge, thus maintaining the corona discharge of
the discharge electrode as a whole. An ion current output also
remains stable.
Alternatively, even if some of the needle electrodes 31 deposited
with organic compounds stop their corona discharge, the potentials
of the stopped discharge needle electrodes rise while the remaining
needle electrodes continue the corona discharge, so that the
deposited compounds are destroyed and dispersed by discharge
breakdown and the stopped discharge needle electrodes thereby
resume their corona discharge. Even if deposition and dispersion of
organic compounds are repeated at some needle electrodes the
discharge electrode 25 as a whole can maintain a stable corona
discharge for a long period.
Stopping and resuming of corona discharge by the discharge
electrode occurs also in the case of a conventional single needle
electrode discharging at a single point. However, in this case, the
discharge completely stops during this period. Thus, a stable
corona discharge and stable ion current output are not
possible.
Shown in FIG. 6 is a measurement result of an ion output current I
with this embodiment, using lipids such as monogalactosly diachyl
glycerol as solutes. As apparent from FIG. 6, the fluctuation range
.DELTA.I' of an ion current output is extremely small as compared
with a conventional one shown in FIG. 3, thus enabling the
detection of the components (4) and (5) of the specimen. In other
words, an S/N (signal to noise) ratio of an ion current output is
considerably improved.
Another example of a multiple point discharge electrode used in
this invention will be described with reference to FIGS. 7A and
7B.
An elongated wire of tungsten, rhenium or the like is generally
formed with micro concavities and convexities on the
circumferential surface during manufacturing. By using concavities
as the discharge points, this elongated fine wire can be used as a
discharge electrode having a plurality of discharge points on the
circumferential surface. The fine wire may preferably have a
diameter of about 20 to 100 .mu.m.
FIGS. 7A and 7B are side and front views of a discharge electrode
using such a fine wire. In the figure, reference numeral 40 denotes
a conductive support made of, e.g., copper, and reference numeral
41 denotes a fine tungsten or rhenium wire. By applying a DC
voltage to the support 40, corona discharge occurs at the fine wire
41. In FIG. 7A, the aperture 18a is assumed as positioned at the
right side.
A further example of a multiple point discharge electrode is shown
in FIGS. 8A to 8C.
In this example, a plurality of whiskers 52 (see FIG. 8C) made of
tungsten, silicon, carbon or the like are grown on the periphery of
a fine wire made of tungsten, rhenium or the like having a diameter
of about 10 to 20 .mu.m, each whisker being used as a discharge
point. Thus, by applying a DC voltage to the support 40, corona
discharge occurs at the tips of the whiskers 52 grown on the
periphery of the fine wire 51.
These whiskers may be ones used as ionization means for mass
analysis in Field Desorption. In FIG. 8A, the aperture 18a is
assumed as positioned at the right side.
A still further example of a multiple point discharge electrode is
shown in FIGS. 9A and 9B.
In this example, a knife edge portion of a safety razor or the like
is used as a multiple point discharge electrode. A knife edge has
micro concavities and convexities, the latter serving as discharge
points. A plurality of discharge points are accordingly disposed
laterally of the knife edge. The number of discharge points may be
multiplied by using a plurality of knife edges. By applying a DC
voltage to the support 40 on which the knife edge 61 is supported,
corona discharge occurs at the knife edge 61. In FIG. 9A, the
aperture 18a is assumed as positioned at the right side.
The discharge electrodes shown in FIGS. 7A and 7B to FIGS. 9A and
9B have similar operation and effect to those of the discharge
electrode shown in FIGS. 5A and 5B.
According to the present invention, a discharge electrode is
constructed of a multiple point discharge electrode structure so
that even if one discharge point is deposited with organic
compounds and its discharge is stopped, the corona discharge of the
discharge electrode as a whole does not become unstable. Therefore,
even under an atmosphere containing a large number of organic
compounds mass analysis can be performed stably and with high
sensitivity.
Further, even if one discharge point deposited with organic
compounds stop its discharge, the potential of the discharge
stopped point rises while the remaining discharge points hold the
corona discharge, so that the corona discharge from the once
discharge stopped point will resume, to thus improve the overall
discharge stability.
In the above embodiments, the description has been directed to the
case where the atmospheric pressure ionization mass spectrometer of
this invention is applied to the LC/MS system shown in FIG. 1.
However, the invention may be applied to a system with LC 1 and the
spray/vapor chamber 3 shown in FIG. 1 removed therefrom. In this
case, gas of vaporized organic substances or the like is introduced
into the inlet 11 shown in FIG. 4. Further, in the present
invention, solutes are not limited to organic compounds but other
substances may be used.
* * * * *